Field of the Invention
The present invention relates to a method of determining a dose of an erythropoiesis-stimulating agent, and particularly to a method of advantageously determining a dose of an erythropoiesis-stimulating agent, which dose allows a hemoglobin concentration in the blood to be stably maintained at a target value.
Description of Related Art
It is known that in a patient with renal failure suffering from deterioration of the kidney, erythropoietin is not produced or an amount of production of erythropoietin is extremely reduced, resulting in reduction of production of red blood cells, since the production of the red blood cells in the bone marrow is stimulated by erythropoietin mainly produced in the kidney, so that the patient with renal failure suffers from severe anemia, so-called renal anemia.
In order to supply erythropoietin to the patient with renal anemia such as a hemodialysis patient, an erythropoiesis-stimulating agent (ESA) is administered to the patient. The ESA is an erythropoietin preparation prepared by gene recombination, and includes first generation medical agents such as epoetin α and epoetin β (EPO) and a second generation medical agent such as darbepoetin α (DA). The above-indicated medical agents are intravenously administered to the hemodialysis patient through the blood circuit at the time of termination of hemodialysis, for example. At this time, a dose of the ESA is determined based on a doctor's experience such that a hemoglobin concentration in the blood reaches a proper value (10-11 g/dL) set according to guidelines of academic societies. However, the ESA dose determined based on the doctor's experience is sometimes excessively high or excessively low, so that the hemoglobin concentration in the blood inevitably fluctuates over a wide range. It has been difficult to decrease the range of fluctuation of the hemoglobin concentration.
In the case where the hemoglobin concentration in the blood becomes excessively high due to an excessively high ESA dose, there arise not only a problem of an increase in a cost of medical treatment of the patient due to an increase in an amount of use of the costly ESA, but also a problem of an increase in a risk of death of the patient. The problem of an increase in the risk of death also arises where the hemoglobin concentration in the blood becomes excessively low due to an excessively low ESA dose. Further, it is reported that the larger an amount of fluctuation of the hemoglobin concentration in the blood, the higher the risk of death (see Yang W, et al.: J. Am. Soc. Nephrol. 18: 3164-3170, 2007.).
In order to solve the above-described problems caused by the determination of the ESA dose based on the doctor's experience, there was made an algorithm for determining the ESA dose based on a difference between a target value and a present value of the hemoglobin concentration, and a past ESA dose, such that an actually measured value of the hemoglobin concentration will match the target value at the next measurement of the hemoglobin concentration. Namely, according to the algorithm, in the case where the present value of the hemoglobin concentration is lower than the target value, the ESA dose is increased according to the difference therebetween, whereas in the case where the present value of the hemoglobin concentration is higher than the target value, the ESA dose is reduced according the difference therebetween (see Fishbane 5, et al.: Kidney Int. 68: 1337-1343, 2005.). However, the above-described technique still causes fluctuation of the actually measured value of the hemoglobin concentration over a wide range, excessively above or excessively below the target value, so that it has been difficult to decrease the range of fluctuation.
Further, there is reported a method of determining the ESA dose, which is employed where the hemoglobin concentration is measured once per month. In this method, the hemoglobin concentration to be achieved one month later is estimated from the hemoglobin concentrations respectively measured one month ago and at the present moment, and in the case where the hemoglobin concentration estimated to be achieved one month later is lower than the target value of the hemoglobin concentration, the ESA dose is increased according to a difference therebetween, whereas in the case where the hemoglobin concentration estimated to be achieved one month later is higher than the target value, the ESA dose is reduced according to a difference therebetween (see Lines S W, et al.: Nephrol. Dial. Transplant. 27: 2425-2429, 2012.). However, according to the above-described method of determination of the ESA dose so as to decrease the difference between the hemoglobin concentration estimated to be achieved one month later and the target value, it has been impossible to sufficiently decrease the range of fluctuation of the actually measured value of the hemoglobin concentration above or below the target value.